For example, in VHL-defective RCC cells, oncoprotein HDM2 not only affects constitutively expressed HIFα, but also directly regulates protein levels of HIF angiogenic targets (e.g., VEGF, PA inhibitor-1 (PAI-1), and endothelin-1 (ET-1)) [92]. The gene discussed is EDN1; the disease is renal cell carcinoma.